Food and water borne infectious diseases are a significant source of morbidity and mortality world-wide. Children are especially at risk from these infections. Although often assumed to be only a problem in developing areas of the world, bacterial infections of the gastro-intestinal tract remain a serious source of disease in the US. Our long-term goal is to understand both host-response and host pathogen interactions in the gut to Yersinia enterocolitica that lead to resolution of infection or to pathology. Y. enterocolitica is an excellent pathogen to use in our studies as it has served as one of the paradigms of bacterial infectious diseases. In this proposal we expand our studies to look at the role of IL-6 in the modulation of the host response during Y. enterocolitica infection. We hypothesize that IL-6 may be a crucial regulator of inflammatory responses to infection by influencing the cytokine response of host cells involved in response to Y. enterocolitica infection. We also hypothesize that the IL-6 mediated tempering of inflammatory responses may be triggered by Y. enterocolitica encoded molecules. To test these hypotheses we propose the following specific aims: 1) Identify the cells producing IL-6 in response to Y. enterocolitica infection and 2) the cells responding to IL-6 during infection in the Peyer's patch, mesenteric lymph node, and spleen. These data will give us insight into which host cells are modulating the host response to infection. 3) Test the contribution of the IL-6 modulated cytokines to the immunopathogenesis of intestinal yersiniosis. Mice deficient in IL-6 have distinct cytokine expression profiles and many of these cytokines are critical to the resolution of disease but it is unknown how mis-regulation of these cytokines contributes to pathology. These data will explore the connection between IL-6 mediated modulation of the immune response and Yersinia virulence. Altogether, these data will give us insight into how IL-6 contributes to the pathogenesis of Yersinia infection and how immune pathologies are prevented during self limiting infections. These data may provide insight into the etiology of chronic intestinal inflammation.